Field of the Invention
The present invention relates to the therapeutic treatment of proliferation-type skin diseases. More particularly, the present invention relates to the use of corticosteroids in combination with 5-fluorouracil in the treatment of skin conditions such as psoriasis.
Psoriasis is a common, chronic, relapsing disease of unknown etiology which consists of elevated, silvery, dry lesions which are known as plaques. Pathologically, there are three obvious changes associated with the disease: (1) increase in the rate of cell division of the epidermis, (2) striking increase in the thickness of the cornified epithelium, and (3) proliferation of the subepithelial capillaries.
Corticosteroids and especially halogenated corticosteroids have been successfully used in the topical treatment of psoriasis to temporarily alleviate the signs and symptoms of the disease. This effect is probably due to influence on the nucleic acid metabolism of the epidermis. The effect, which is most striking when occlusive dressings are used, is now well documented and accepted. However, there are several disadvantages with this type of treatment: occlusion must go on for periods of up to 2-3 weeks before lesions are cleared; and the recurrence rate is high, that is, the lesions return within a few weeks to a few months after withdrawal of therapy.
5-Fluorouracil has also been used in the topical treatment of psoriatic lesions under occlusion. However, when used alone erosions must be produced in order to have a lasting effect (Tsuji and Sugai, Arch. Derm., 105:208, 1973), and these erosions are painful to the patient. 5-Fluorouracil is a known inhibitor of thimydylate synthetase and through this inhibition also interferes with the nucleic acid metabolism.